Project description:Genome wide DNA methylation profiling in saliva samples from individuals with and without coeliac disease. The Illumina Infinium 450k Human DNA methylation BeadChip was used to obtain DNA methylation profiles across approximately 485,500 CpGs. The study investigated DNA methylation profiles associated with CD.
Project description:BackgroundCoeliac disease (CD) is a autoimmune disease characterised by mucosal inflammation in the small intestine in response to dietary gluten. Genetic factors play a key role with CD individuals carrying either the HLA-DQ2 or HLA-DQ8 haplotype, however these haplotypes are present in half the general population making them necessary but insufficient to cause CD. Epigenetic modifications, including DNA methylation that can change in response to environmental exposure could help to explain how interactions between genes and environmental factors combine to trigger disease development. Identifying changes in DNA methylation profiles in individuals with CD could help discover novel genomic regions involved in the onset and development of CD.MethodsThe Illumina InfiniumMethylation450 Beadchip array (HM450) was used to compare DNA methylation profiles in saliva, in CD and non-CD affected individuals. CD individuals who had been diagnosed at least 2 years previously; were on a GFD; and who were currently asymptomatic; were compared to age and sex-matched non-CD affected healthy controls. Bisulphite pyrosequencing was used to validate regions found to be differentially methylated. These regions were also validated in a second larger cohort of CD and non-CD affected individuals.ResultsMethylation differences within the HLA region at HLA-DQB1 were identified on HM450 but could not be confirmed with pyrosequencing. Significant methylation differences near the SLC17A3 gene were confirmed on pyrosequencing in the initial pilot cohort. Interestingly pyrosequencing sequencing of these same sites within a second cohort of CD and non-CD affected controls produced significant methylation differences in the opposite direction.ConclusionAltered DNA methylation profiles appear to be present in saliva in CD individuals. Further work to confirm whether these differences are truly associated with CD is needed.
Project description:Cardiovascular disease (CVD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Monocytes play a major role in the initiation, propagation, and progression of CVD. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. The aim of this study was to investigate whether differences in miRNA expression levels in monocytes can be found (i) between patients with premature CVD and healthy controls, (ii) within healthy controls after and before aspirin and statin administration, and (iii) between current, former and non smokers.
Project description:Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. The aim of this study was to investigate whether differences in miRNA expression levels in platelets can be found (i) between patients with premature CAD and healthy controls and (ii) within healthy controls after and before aspirin and statin administration.
Project description:Genome-wide methylation profiling performed on whole blood DNA samples from three groups: 1 - Dialysis patients at baseline (before treatment) and after 12 months of dialysis (n=12) 2 - Renal transplant patients at baseline (before treatment) and after 12 months of dialysis (n=12) 3 - Healthy controls (one time-point only) (n=24) All groups matched for gender and age
Project description:Background: The molecular pathogenesis of small intestinal adenocarcinomas (SBA) is not well understood. Defining its molecular pathogenesis may lead us to better clinical interventions. Aim: to identify the molecular changes characteristic of SBA. Methods: Forty-eight SBA (thirty-three non coeliac disease (CD)-related and 15 CD-related) were characterized for chromosomal aberrations, by high resolution array comparative hybridization (aCGH), microsatellite status (MSI) and APC promoter methylation and mutation status. Furthermore, molecular alterations found in CD-related SBA were compared to non-CD related SBA. Results: Chromosomal changes were observed in 77% of the SBA. The most frequently (>10%) DNA copy number changes found were gains on 5p15.33-5p12, 7p22.3-7q11.21, 7q21.2-7q21.3, 7q22.1-7q34, 7q36.1, 7q36.3, 8q11.21-8q24.3, 9q34.11-9q34.3, 13q11-13q34, 16p13.3, 16p11.2, 19q13.2 and 20p13-20q13.33 and losses of 4p13-4q35.2, 5q15-5q21.1 and 21p11.2-21q22.11. Seven highly amplified regions on 6p21.1, 7q21.1, 8p23.1, 11p13, 16p11.2, 17q12-q21.1 and 19q13.2 were also identified. CD-related and non CD-related SBA displayed similar chromosomal aberrations. Promoter hypermethylation of the APC gene was found in 48% non CD-related and 73% CD-related SBA. No nonsense mutations were found. Last, 10% of the non CD-related SBA were MSI, whereas 43% of the CD-related SBA were MSI. Conclusions: Our study characterized specific chromosomal aberrations and amplifications involved in SBA pathogenesis. At the chromosomal level, CD-related and non CD-related SBA do not differ. The involvement of the MMR system in the pathogenesis of the CD-related SBA was larger than what has been observed in no CD-related SBA. No nonsense mutations were found in SBA, but frequent promoter methylation in CD-related SBA. Forty-eight SBA (thirty-three non coeliac disease (CD)-related and 15 CD-related) were characterized for chromosomal aberrations against a Human pool, by high resolution array comparative hybridization (aCGH),